Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): An open-label, single-arm, phase 3 trial Journal Article


Authors: Kleinmann, N.; Matin, S. F.; Pierorazio, P. M.; Gore, J. L.; Shabsigh, A.; Hu, B.; Chamie, K.; Godoy, G.; Hubosky, S.; Rivera, M.; O'Donnell, M.; Quek, M.; Raman, J. D.; Knoedler, J. J.; Scherr, D.; Stern, J.; Weight, C.; Weizer, A.; Woods, M.; Kaimakliotis, H.; Smith, A. B.; Linehan, J.; Coleman, J.; Humphreys, M. R.; Pak, R.; Lifshitz, D.; Verni, M.; Adibi, M.; Amin, M. B.; Seltzer, E.; Klein, I.; Konorty, M.; Strauss-Ayali, D.; Hakim, G.; Schoenberg, M.; Lerner, S. P.
Article Title: Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): An open-label, single-arm, phase 3 trial
Abstract: Background: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel. Methods: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5–15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4–6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128. Findings: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47–71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1–12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. Interpretation: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients. Funding: UroGen Pharma. © 2020 Elsevier Ltd
Keywords: adult; treatment outcome; aged; aged, 80 and over; middle aged; clinical trial; united states; cancer grading; drug effect; pathology; kidney neoplasms; time factors; urothelium; kidney tumor; multicenter study; carcinoma; israel; phase 3 clinical trial; antibiotics, antineoplastic; mitomycin; antineoplastic antibiotic; drug carrier; drug carriers; drug formulation; time factor; drug compounding; hydrogel; neoplasm grading; hydrogels; very elderly; humans; human; male; female
Journal Title: Lancet Oncology
Volume: 21
Issue: 6
ISSN: 1470-2045
Publisher: Elsevier Science, Inc.  
Date Published: 2020-06-01
Start Page: 776
End Page: 785
Language: English
DOI: 10.1016/S1470-2045(20)30147-9
PUBMED: 32631491
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 August 2020 -- Source: Scopus
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  1. Jonathan Coleman
    279 Coleman